Photoacoustic (PA) tomography [1] and thermoacoustic (TA) tomography [2] (hereafter referred as PAT/TAT) have been developed as hybrid biomedical imaging modalities suitable for applications in bioimaging. PAT/TAT combines the advantages of pure ultrasound and pure optical/radio frequency (rf) imaging, providing good spatial resolution, great penetration depth, and high soft-tissue contrast. These imaging modalities are based on the detection of acoustic waves from an object that absorbs electromagnetic energy (for example, a PAT system uses laser whereas a TAT system uses a microwave excitation source). Recently, high resolution PAT and/or TAT have been used for advanced imaging applications such as functional brain imaging [3,4], early breast cancer detection [5,6], melanoma detection [7,8], tumor angiogenesis [9,10] and functional molecular imaging [11].
The development of PAT and TAT as hybrid biomedical imaging modalities has led concurrently to increased use of chemical contrast-enhancement products called contrast agents (CAs) which improve detection of pathologic lesions by increasing sensitivity and diagnostic confidence. For example, it is known that optical absorption in biological tissues is due to or induced by endogenous molecules such as hemoglobin, melanin, and water/ion. However, in the cases when endogenous molecules are insufficient, exogenous contrast agents would have to be administered. Contrast-enhanced PAT imaging can be used for non-invasive characterization of levels of vascularization and oxygen saturation of tissues and serves as tool to monitor tissue regeneration. In particular, contrast-enhanced PAT has been applied in lymph node mapping [12], multiscale imaging of tissue engineering scaffolds [13-15], and molecular, cellular, and functional imaging [16-19]. A variety of contrast agents for PAT have been reported, such as, carbon nanoparticles [12, 20-22], metallic nanoparticles [17-19, 23-25], and organic dyes [26]. In comparison to PAT, fewer reports have focused on development of contrast agents for TAT in biomedical applications. Among them, superparamagnetic iron oxide nanoparticles, and single- and multi-walled carbon nanotubes (SWCNT and MWCNT) have been investigated as TA contrast agents [2, 21].
Most recently, oxidized graphene nanoplatelets (O-GNPs) and oxidized graphene nanoribbons (O-GNRs) have also been reported as contrast agents for other whole-body imaging applications such as magnetic resonance imaging [28] and nuclear imaging [32]. The results of these and other reports suggest the possibility of their development as multimodal contrast agents that provide complementary information at micro- to macro-scopic length scales. Furthermore, these graphene nanoparticles can be functionalized for targeted therapeutics, drug delivery and cellular/molecular imaging applications [33], and thus, show potential as multifunctional nanoparticles. Indeed, several in vitro and in vivo safety and efficacy studies on these graphene nanoparticles have been reported for various biomedical applications [29,33,41].